A UW-Madison researcher and colleagues have developed methods of using probiotic bacteria engineered to express IL-22 or IFN-β, alone or in combination with an immune checkpoint therapy and/or an irradiation therapy, for oral treatment of cancer. The inventors have demonstrated a further use for Dr. van Pijkeren’s genetically-engineered gastrointestinal tract (GI) bacterium (e.g., Lactobacillus reuteri) that releases interleukin-22 (e.g., LR-IL-22). Both LR-IL-22 and ionizing irradiation each induce the PD-L1 immunotherapy target in ovarian cancer cells, and the combination of radiation and LR-IL-22 significantly increases numbers of infiltrating CD8+ T-cells and other beneficial immunocytes in ovarian cancer tumors. Dr. van Pijkeren produced the bacteria used for the method, and Dr. Greenberger discovered that recombinant L. reuteri can be isolated from ovarian tumors following oral administration.